The human cardiovascular system is an intricate, complex network of blood vessels that include arteries, capillaries and veins. These structures distribute blood from the heart to all parts of the body, from our head to our toes, and back again.
This week, two groups of scientists published studies showing that they can create key components of the human cardiovascular system from human pluripotent stem cells. These technologies will not only be valuable for modeling the cardiovascular system, but also for developing transplantable tissues to treat patients with cardiovascular or vascular diseases.
Growing capillaries using 3D printers
Scientists from Rice University and the Baylor College of Medicine are using 3D printers to make functioning capillaries. These are tiny, thin vessels that transport blood from the arteries to the veins and facilitate the exchange of oxygen, nutrients and waste products between the blood and tissues. Capillaries are made of a single layer of endothelial cells stitched together by cell structures called tight junctions, which create an impenetrable barrier between the blood and the body.
In work published in the journal Biomaterials Science, the scientists discovered two materials that coax human stem cell-derived endothelial cells to develop into capillary-like structures. They found that adding mesenchymal stem cells to the process, improved the ability of the endothelial cells to form into the tube-like structures resembling capillaries. Lead author on the study, Gisele Calderon, explained their initial findings in an interview with Phys.org,
“We’ve confirmed that these cells have the capacity to form capillary-like structures, both in a natural material called fibrin and in a semisynthetic material called gelatin methacrylate, or GelMA. The GelMA finding is particularly interesting because it is something we can readily 3-D print for future tissue-engineering applications.”
Scientists grow capillaries from stem cells using 3D gels. (Image Credit: Jeff Fitlow/Rice University)
The team will use their 3D printing technology to develop more accurate models of human tissues and their vast network of capillaries. Their hope is that these 3D printed tissues could be used for more accurate drug testing and eventually as implantable tissues in the clinic. Co-senior author on the study, Jordan Miller, summarized potential future applications nicely.
“Ultimately, we’d like to 3D print with living cells … to create fully vascularized tissues for therapeutic applications. You could foresee using these 3D printed tissues to provide a more accurate representation of how our bodies will respond to a drug. The potential to build tissue constructs made from a particular patient represents the ultimate test bed for personalized medicine. We could screen dozens of potential drug cocktails on this type of generated tissue sample to identify candidates that will work best for that patient.”
Growing functioning arteries
In a separate study published in the journal PNAS, scientists from the University of Wisconsin-Madison and the Morgridge Institute reported that they can generate functional arterial endothelial cells, which are cells that line the insides of human arteries.
The team used a lab technique called single-cell RNA sequencing to identify important signaling factors that coax human pluripotent stem cells to develop into arterial endothelial cells. The scientists then used the CRISPR/Cas9 gene editing technology to develop arterial “reporter cell lines”, which light up like Christmas trees when candidate factors are successful at coaxing stem cells to develop into arterial endothelial cells.
Arterial endothelial cells derived from human pluripotent stem cells. (The Morgridge Institute for Research)
Using this two-pronged strategy, they generated cells that displayed many of the characteristic functions of arterial endothelial cells found in the body. Furthermore, when they transplanted these cells into mice that suffered a heart attack, the cells helped form new arteries and improved the survival rate of these mice significantly. Mice who received the transplanted cells had an 83% survival rate compared to untreated mice who only had a 33% survival rate.
In an interview with Genetic Engineering & Biotechnology News, senior author on the study James Thomson, explained the significance of their findings,
“Our ultimate goal is to apply this improved cell derivation process to the formation of functional arteries that can be used in cardiovascular surgery. This work provides valuable proof that we can eventually get a reliable source for functional arterial endothelial cells and make arteries that perform and behave like the real thing.”
In the future, the scientists have set their sights on developing a universal donor cell line that can treat large populations of patients without fear of immune rejection. With cardiovascular disease being the leading cause of death around the world, the demand for such a stem cell-based therapy is urgent.